The invention relates to a process of preparing [S-(R*,S*)]-xcex2-[[[1-[1-oxo-3-(4-piperidinyl)propyl]-3-piperidinyl]carbonyl]amino]-3-pyridinepropanoic acid derivatives represented by the formula 
wherein R1 and R2 are independently selected from hydrogen, lower alkyl and halogen.
The compounds of formula I and method of making and using the compounds of formula I are described in WO 97/41102, Nov. 6, 1997.
Compounds of formula I are antagonists of the platelet fibrinogen receptor (GP 11b/111a antagonist). Thus, the compounds of formula I are useful for the treatment of thrombotic disorders such as restenosis post-angioplasty, unstable/stable angina and myocardial infarction.
A known method of the preparation of a compound of formula I is disclosed in WO 97/41102 involving coupling of enantiomerically enriched methyl (S)-3-amino-3-pyridylpropanoate with N-(t-butoxycarbonyl)-(R)-nipecotic acid followed by removal of the N-t-butoxycarbonyl protecting group under acidic conditions and coupling with 3-(N-t-butoxycarbonyl-4-piperidyl)propionic acid. The crude ester product is then hydrolyzed using aqueous LiOH and the N-t-butoxycarbonyl amino protecting group is removed under acidic conditions with trifluoroacetic acid (xe2x80x9cTFAxe2x80x9d). The bis-TFA salt is isolated as a white amorphous solid.
A process for preparing N-(3-piperidinyl carbonyl)-xcex2-alanine derivatives is disclosed in WO 95/08536.
The current invention relates to a more efficient process of preparing compounds of formula I.